Potential Susceptibility Variants for Obesity and Type 2 Diabetes in the TALLYHO Mouse
Year: 2012
Type: article
Abstract: The TALLYHO/Jng (TH) mouse is an inbred polygenic model for Type 2 diabetes characterized by obesity, insulin resistance, hyperlipidemia, and hyperglycemia. Genetic outcross experiments with lean non-diabetic strain of C57BL/6 (B6) mice revealed major susceptibility loci for obesity on chromosome 6 (Tabw2) and for diabetes on chromosome 4 (Tanidd4). For both loci, the TH alleles are associated with disease susceptibilities. Currently, the Tabw2 locus has been fine mapped to 8-Mb interval and the Tanidd4 locus to 15.8-Mb interval. In order to identify potential susceptibility variants for Tabw2 and Tanidd4 loci, we performed whole genome sequencing of the TH mouse genome in two 2 x 100 paired end read strategies using an Illumina HiSeq1000 next generation sequencer. Libraries were prepared and sequenced using standard Illumina protocols. We generated ∼60 Gb of TH sequence with an average coverage of ∼25X. Seventy five percent of the readout aligned to the mouse reference B6 genome (Build 37). In our initial test, we compared the TH genome to the B6 genome using Illumina CASAVA software and identified 4,749,554 SNPs. Among the SNPS, 38,147 mapped to the Tabw2 interval and 83,122 to the Tanidd4 interval. In order to refine these sets, we compared the TH, which contains Swiss lineage, variant set to those variants in three Swiss-derived non-obese, non-diabetic strains (A/J, AKR/J and Balb/cJ). We identified 17,360 SNPs and 28,297 SNPS within the Tabw2 and Tanidd4 intervals, respectively, that were not found in any of the three non-diabetic strains. In conclusion, we applied a whole-genome sequencing strategy in combination with mapping information to identify a set of candidate genes for the obese and diabetic phenotypes in TH mice. Further defined and systemic filtration of the variants (e.g. based on variant effect of function) will facilitate identification of the causal genes and variants.
Source: Europe PMC (PubMed Central)
Institution: Marshall University
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2411453197